(1) Summary of the Invention
The present invention relates to the isolation and purification of novel potent antifungal compounds belonging to the anthracycline group of antibiotics. In particular the present invention relates to antifungal compounds produced by Micromonospora spartanea (ATCC 53803), a new species of Micromonospora.
(2) Prior Art
Micromonospora species are well known for their ability to produce biologically active compounds. Calicheamicin, approximately 1000-fold more active than adriamycin against murine tumors, is an unusually powerful antitumor compound isolated from M. echinospora ssp. Calichenis (Lee, M. D., et al., J. Am. Chem. Soc. 109:3464 (1987); Lee, M. D., et al., J. Am. Chem. Soc. 109:3466 (1987); and Golik, J., et al., J. Am. Chem. Soc. 109:3461 (1987)). Triglycosidic antibiotics, isolated from M. inositola and M. megalomicea (White, H. B., et al., J. Biol. Chem., 243, 4517 (1960); DeRosa, M., et al., J. Chem. Soc. Chem. Commun. p. 619 (1971); Nair, M. S. R., et al., Tetrahedron Lett., p. 1655 (1975); and Nair, M. S. R., et al., Tetrahedron Lett. p. 1267 (1975)). Other antibiotics reported from Micromonospora species are chalcidin complex, everninomicin B and D (Wagman, G. H., et al., Antimicrob. Agents Chemother., p. 33 (1964); Ganguly, A. K., et al., Chem. Commun. p. 531 ( 1973); and Ganguly, A. K., et al, J. Am. Chem. Soc. 97, 1982 (1975)) and ferrioxamine B (Zahner, H., et al., J. Pathol. Microbiol., 25, 708 (1962); Muller, A., et al., Arch. Mikrobiol. 62, 250 (1968); Bickel, H., et al., Helv. Chem. Acta., 2129 (1960); Prelog, V., et al., Helv. Chim. Acta., 45, 631 (1962); and Bickel, H., Helv. Chim. Acta, 46, 1385 (1963)).
Micromonospora spp. are also known to produce compounds similar to those obtained from Streptomyces spp. (Kondo, S., et al., J. Antibiot. (Tokyo), 30, 1137 (1977); and Kondo, S., et al., J. Antibiot. (Tokyo), 24, 732 (1971)). Streptomyces galilaeus produces 21 anthracycline antibiotics out of which aclacinomycin A, B, and their derivatives were studied for their antitumor activities (Oki, T., et al., J. Antibiotics, 28, 830 (1975); Oki, T., et al., J. Antibiotics, 30, 683 (1977); Oki, T., Jap. J. Antibiotics, 30, S70 (1977); Oki, T., et al., J. Antibiotics, 32, 791 (1979); Oki, T., et al., J. Antibiotics, 32, 801 (1979); Soga, K., et al., J. Antibiotics, 770 (1971); Tanaka, H., et al., J. Antibiotics, 34, 905 (1981); and Matsuzawa, Y., et al., J. Antibiotics, 34, 1596 (1981)). It is not known that antifungal compounds could be produced by this species.
Related patents describing anthracycline glycosides are U.S. Pat. No. 3,988,315 to Umezawa et al; U.S. Pat. No. 4,209,588 to Umezawa et al; U.S. Pat. No. 4,245,045 to Umezawa et al; U.S. Pat. No. 4,375,511 to Fujiwara et al and U.S. Pat. No. 4,383,037 to Fujiwara et al.